Role of BacA in Lipopolysaccharide Synthesis, Peptide Transport, and Nodulation by \u3cem\u3eRhizobium\u3c/em\u3e sp. Strain NGR234

BacA of Sinorhizobium meliloti plays an essential role in the establishment of nitrogen-fixing symbioses with Medicago plants, where it is involved in peptide import and in the addition of very-long-chain fatty acids (VLCFA) to lipid A of lipopolysaccharide (LPS). We investigated the role of BacA in Rhizobium species strain NGR234 by mutating the bacA gene. In the NGR234 bacA mutant, peptide import was impaired, but no effect on VLCFA addition was observed. More importantly, the symbiotic ability of the mutant was comparable to that of the wild type for a variety of legume species. Concurrently, an acpXL mutant of NGR234 was created and assayed. In rhizobia, AcpXL is a dedicated acyl carrier protein necessary for the addition of VLCFA to lipid A. LPS extracted from the NGR234 mutant lacked VLCFA, and this mutant was severely impaired in the ability to form functional nodules with the majority of legumes tested. Our work demonstrates the importance of VLCFA in the NGR234-legume symbiosis and also shows that the necessity of BacA for bacteroid differentiation is restricted to specific legume-Rhizobium interactions

The effect of population density on shoot morphology of herbs in relation to light capture by leaves

Plants change their shapes, depending on their environment, for example, plant height increases with increasing population density. We examined the density-dependent plasticity in shoot morphology of herbs by analysing a mathematical model which identifies a number of key factors that influence shoot morphology, namely (i) solar radiation captured by leaves; (ii) shading from neighbouring plants; and (iii) utilisation efficiency of resource by leaves, stems and veins. An optimisation theory was used to obtain optimal shoot morphology in relation to maximal light capture by leaves, under trade-offs of resource partition among organs. We first evaluated the solar radiation flux per unit leaf area per day for different shoot forms. Our model predicts that the optimal internodal length of the stem that brings about the maximal light capture by leaves increases with plant population density, and this is consistent with experimental data. Moreover, our simple model can also be extended to explain the morphological plasticity in other herbs (i.e. stemless plants) that are different from our model plants with a stem. These findings illustrate how optimisation theory can be used for the analysis of plasticity in shoot morphology of plants in response to environmental changes, as well as the analysis of diversity in morphology

TCR-engineered adoptive cell therapy effectively treats intracranial murine glioblastoma

BACKGROUND: Adoptive cellular therapies with chimeric antigen receptor T cells have revolutionized the treatment of some malignancies but have shown limited efficacy in solid tumors such as glioblastoma and face a scarcity of safe therapeutic targets. As an alternative, T cell receptor (TCR)-engineered cellular therapy against tumor-specific neoantigens has generated significant excitement, but there exist no preclinical systems to rigorously model this approach in glioblastoma. METHODS: We employed single-cell PCR to isolate a TCR specific for the Imp3 RESULTS: We isolated and characterized the 3×1.1C TCR that displayed a high affinity for mImp3 but no wild-type cross-reactivity. To provide a source of mImp3-specific T cells, we generated the MISTIC mouse. In a model of adoptive cellular therapy, the infusion of activated MISTIC T cells resulted in rapid intratumoral infiltration and profound antitumor effects with long-term cures in a majority of GL261-bearing mice. The subset of mice that did not respond to the adoptive cell therapy showed evidence of retained neoantigen expression but intratumoral MISTIC T cell dysfunction. The efficacy of MISTIC T cell therapy was lost in mice bearing a tumor with heterogeneous mImp3 expression, showcasing the barriers to targeted therapy in polyclonal human tumors. CONCLUSIONS: We generated and characterized the first TCR transgenic against an endogenous neoantigen within a preclinical glioma model and demonstrated the therapeutic potential of adoptively transferred neoantigen-specific T cells. The MISTIC mouse provides a powerful novel platform for basic and translational studies of antitumor T-cell responses in glioblastoma

Stellar population and dust extinction in an ultraluminous infrared galaxy at z=1.135

We present the detailed optical to far-infrared observations of SST J1604+4304, an ULIRG at z = 1.135. Analyzing the stellar absorption lines, namely, the CaII H & K and Balmer H lines in the optical spectrum, we derive the upper limits of an age for the stellar population. Given this constraint, the minimum {chi}^2 method is used to fit the stellar population models to the observed SED from 0.44 to 5.8um. We find the following properties. The stellar population has an age 40 - 200 Myr with a metallicity 2.5 Z_{sun}. The starlight is reddened by E(B-V) = 0.8. The reddening is caused by the foreground dust screen, indicating that dust is depleted in the starburst site and the starburst site is surrounded by a dust shell. The infrared (8-1000um) luminosity is L_{ir} = 1.78 +/- 0.63 * 10^{12} L_{sun}. This is two times greater than that expected from the observed starlight, suggesting either that 1/2 of the starburst site is completely obscured at UV-optical wavelengths, or that 1/2 of L_{ir} comes from AGN emission. The inferred dust mass is 2.0 +/- 1.0 * 10^8 M_{sun}. This is sufficient to form a shell surrounding the galaxy with an optical depth E(B-V) = 0.8. From our best stellar population model - an instantaneous starburst with an age 40 Myr, we infer the rate of 19 supernovae(SNe) per year. Simply analytical models imply that 2.5 Z_{sun} in stars was reached when the gas mass reduced to 30% of the galaxy mass. The gas metallcity is 4.8 Z_{sun} at this point. The gas-to-dust mass ratio is then 120 +/- 73. The inferred dust production rate is 0.24 +/- 0.12 M_{sun} per SN. If 1/2 of L_{ir} comes from AGN emission, the rate is 0.48 +/- 0.24 M_{sun} per SN. We discuss the evolutionary link of SST J1604+4304 to other galaxy populations in terms of the stellar masses and the galactic winds.Comment: 11 pages, 9 figures, accepted for publication in MNRA

Complete blockage of the mevalonate pathway results in male gametophyte lethality

Plants have two isoprenoid biosynthetic pathways: the cytosolic mevalonate (MVA) pathway and the plastidic 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. Since the discovery of the MEP pathway, possible metabolic cross-talk between these pathways has prompted intense research. Although many studies have shown the existence of such cross-talk using feeding experiments, it remains to be determined if native cross-talk, rather than exogenously applied metabolites, can compensate for complete blockage of the MVA pathway. Previously, Arabidopsis mutants for HMG1 and HMG2 encoding HMG-CoA reductase (HMGR) were isolated. Although it was shown that HMGR1 is a functional HMGR, the enzyme activity of HMGR2 has not been confirmed. It is demonstrated here that HMG2 encodes a functional reductase with similar activity to HMGR1, using enzyme assays and complementation experiments. To estimate the contribution of native cross-talk, an attempt was made to block the MVA pathway by making double mutants lacking both HMG1 and HMG2, but no double homozygotes were detected in the progeny of self-pollinated HMG1/hmg1 hmg2/hmg2 plants. hmg1 hmg2 male gametophytes appeared to be lethal based on crossing experiments, and microscopy indicated that ∼50% of the microspores from the HMG1/hmg1 hmg2/hmg2 plant appeared shrunken and exhibited poorly defined endoplasmic reticulum membranes. In situ hybridization showed that HMG1 transcripts were expressed in both the tapetum and microspores, while HMG2 mRNA appeared only in microspores. It is concluded that native cross-talk from the plastid cannot compensate for complete blockage of the MVA pathway, at least during male gametophyte development, because either HMG1 or HMG2 is required for male gametophyte development

HerMES: dust attenuation and star formation activity in ultraviolet-selected samples from z 4 to 1.5

We study the link between observed ultraviolet (UV) luminosity, stellar mass and dust attenuation within rest-frame UV-selected samples at z ∼ 4, ∼ 3 and ∼1.5. We measure by stacking at 250, 350 and 500μm in the Herschel/Spectral and Photometric Imaging Receiver images from the Herschel Multi-Tiered Extragalactic Survey (HerMES) program the average infrared luminosity as a function of stellar mass and UV luminosity. We find that dust attenuation is mostly correlated with stellar mass. There is also a secondary dependence with UV luminosity: at a given UV luminosity, dust attenuation increases with stellar mass, while at a given stellar mass it decreases with UV luminosity. We provide new empirical recipes to correct for dust attenuation given the observed UV luminosity and the stellar mass. Our results also enable us to put new constraints on the average relation between star formation rate (SFR) and stellar mass at z ∼ 4, ∼3 and ∼1.5. The SFR–stellar mass relations are well described by power laws (SFR ∝ M 0.7∗), with the amplitudes being similar at z ∼ 4 and ∼3, and decreasing by a factor of 4 at z ∼ 1.5 at a given stellar mass. We further investigate the evolution with redshift of the specific SFR. Our results are in the upper range of previous measurements, in particular at z ∼ 3, and are consistent with a plateau at 3 < z < 4. Current model predictions (either analytic, semi-analytic or hydrodynamic) are inconsistent with these values, as they yield lower predictions than the observations in the redshift range we explore. We use these results to discuss the star formation histories of galaxies in the framework of the main sequence of star-forming galaxies. Our results suggest that galaxies at high redshift (2.5 < z < 4) stay around 1 Gyr on the main sequence. With decreasing redshift, this time increases such that z = 1 main-sequence galaxies with 10 8 < M ∗ /Mo < 10 10 stay on the main sequence until z = 0

Global Changes in Staphylococcus aureus Gene Expression in Human Blood

Staphylococcus aureus is a leading cause of bloodstream infections worldwide. In the United States, many of these infections are caused by a strain known as USA300. Although progress has been made, our understanding of the S. aureus molecules that promote survival in human blood and ultimately facilitate metastases is incomplete. To that end, we analyzed the USA300 transcriptome during culture in human blood, human serum, and trypticase soy broth (TSB), a standard laboratory culture media. Notably, genes encoding several cytolytic toxins were up-regulated in human blood over time, and hlgA, hlgB, and hlgC (encoding gamma-hemolysin subunits HlgA, HlgB, and HlgC) were among the most highly up-regulated genes at all time points. Compared to culture supernatants from a wild-type USA300 strain (LAC), those derived from an isogenic hlgABC-deletion strain (LACΔhlgABC) had significantly reduced capacity to form pores in human neutrophils and ultimately cause neutrophil lysis. Moreover, LACΔhlgABC had modestly reduced ability to cause mortality in a mouse bacteremia model. On the other hand, wild-type and LACΔhlgABC strains caused virtually identical abscesses in a mouse skin infection model, and bacterial survival and neutrophil lysis after phagocytosis in vitro was similar between these strains. Comparison of the cytolytic capacity of culture supernatants from wild-type and isogenic deletion strains lacking hlgABC, lukS/F-PV (encoding PVL), and/or lukDE revealed functional redundancy among two-component leukotoxins in vitro. These findings, along with a requirement of specific growth conditions for leukotoxin expression, may explain the apparent limited contribution of any single two-component leukotoxin to USA300 immune evasion and virulence

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations